Each organ in the human body is composed of highly specialized and uniquely shaped cells that serve specific biological roles. Cell volume regulatory mechanisms actively influence physiological systems and functions in an attempt to maintain homeostasis. Changes in cell size are known to alter, for example, metabolism, intracellular signaling pathways, cell cycle progression, nutrient uptake and gene expression. Furthermore, cellular atrophy and hypertrophy are frequently observed as cells respond to a variety of exogenous stressors or pathological conditions. The elucidation of the biological basis of these cell size regulatory mechanisms, across a range of organs and disease states, continues to be a major thrust in biomedical research.
Currently, the vast majority of studies aiming to investigate cell size, in both animals and humans, rely on ex vivo microscopic analysis of perfused organs or tissue sections. While these efforts have made great strides in improving our understanding of cell size regulation and characteristics in disease states they are not suitable for in vivo or longitudinal applications and are often confounded by limited sampling volumes, as in the case of human biopsies. What is needed is a non-invasive imaging method to assess whole organ cell size heterogeneity, as it could provide a valuable tool, in both animals and humans, for tissue and disease characterization, mechanistic explorations, diagnostics and assessment of treatment response.